Methionine abrogates the renoprotective effect of a low-protein diet against diabetic kidney disease in obese rats with type 2 diabetes.

Aging
Munehiro KitadaDaisuke Koya

Abstract

Dietary interventions, including a low-protein diet (LPD) and methionine (Met) restriction, have shown longevity, anti-aging and metabolic health effects. We previously reported that the LPD has a renoprotective effect against diabetic kidney disease (DKD) in rats with type 2 diabetes and obesity. However, it is unclear whether the beneficial effect of the LPD is mediated by low-Met intake or how Met is related to the pathogenesis for DKD. We herein show that the addition of Met with the LPD abrogates the beneficial effects induced by the LPD such as anti-oxidative stress, anti-inflammation and anti-fibrosis, in diabetic kidney. Additionally, the increased levels of S-adenosylmethionine (SAM) in renal tubular cells, which are associated with the reduced expression of glycine N-methyltransferase (Gnmt) and non-restricted Met intake, contributes to the activation of mechanistic target of rapamycin complex 1 (mTORC1) and impaired autophagy, in diabetic kidney. Moreover, starvation-induced autophagy was suppressed in renal cortex of Gnmt null mice and amino acid free-induced autophagy was also suppressed by administration of SAM in cultured HK-2 cells. A LPD could exert a renoprotective effect through the suppression of mTORC1 and ...Continue Reading

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Apr 13, 2019·EBioMedicine·Munehiro KitadaDaisuke Koya

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Citations

May 28, 2020·International Journal of Molecular Sciences·Mark F McCarty, Aaron Lerner
Aug 28, 2020·Frontiers in Cell and Developmental Biology·Munehiro KitadaDaisuke Koya
Nov 4, 2020·The Proceedings of the Nutrition Society·Marina Souza MatosMirela Delibegović
Dec 23, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Yuko KatayamaMasanori Watanabe
Feb 13, 2021·Metabolites·Linda Lauinger, Peter Kaiser
Feb 13, 2021·Biomedicines·Munehiro KitadaDaisuke Koya

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Methods Mentioned

BETA
transmission electron microscopy
urine collection
enzyme-linked immunosorbent assay
ELISA
targeted

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